Animals reared in social isolation exhibit attentional deficits that parallel those found in schizophrenia patients. Such disturbances are frequently attributed to a dysfunction of the mesocortical system. Here we investigated whether electrophysiologic characteristics of prefrontal cortical pyramidal neurons or mesocortical responses were changed in isolated animals. In vivo intracellular recordings were obtained from prefrontal cortical pyramidal neurons in animals raised in social isolation or in socialized control animals before and after ventral tegmental area stimulation mimicking dopamine cell burst firing. Prefrontal cortical pyramidal neurons recorded from isolated animals showed bimodal characteristics resembling those of their socialized littermates. Stimulation of the ventral tegmental area evoked plateau depolarizations in both groups, but this was accompanied by abnormal firing or a short hyperpolarization in most of the isolated animals. These findings suggest that social isolation rearing may affect mesocortical information processing.